Targeted Treatments for Restenosis and Vein Graft Disease

Abstract

Surgery to restore blood flow in arteries blocked by atherosclerotic plaque is a common treatment in cardiovascular disease. Longterm complications of surgical treatment are vein graft disease and restenosis, a renarrowing of the blood vessel after bypass or removal of the culprit atherosclerotic plaque. Attempts to prevent or treat these complications by systemic pharmacological approaches have been largely unsuccessful in the clinic. This has led to an interest in developing targeted or locally delivered strategies. This paper discusses many of the various site-delivered therapies that are under examination as potential antirestenotic and antivein graft disease agents (including antithrombotic, antiproliferative, and anti-inflammatory agents) and why many therapies developed in animal models fail in clinical trials. Techniques of targeted delivery (including stents, "magic bullets," and adventitial delivery) and delivery systems (including nanoparticles and the use of gene therapy) are also discussed.

A multiscale computational framework to understand vascular adaptation

“…Despite the escalating need for these often life-saving procedures, their medium and long-term durability remains compromised. Contemporary data demonstrate restenosis rates following percutaneous coronary interventions to range between 25–35% at 6 months and high grade restenosis (>75%) or occlusion of coronary vein bypass grafts approaching 50% at a year [2]. Since many technical avenues for improved patency have been exhausted, the recent belief has been that the future of enhancing the durability of these constructions lies in a better knowledge of the biology of the vein graft healing response.…”

Techniques in Vascular and Interventional Radiology Drug Delivery Technologies in the Superficial Femoral Artery

“…Several animal studies have looked at perivascular delivery of a variety of compounds, cells, particles in many methods, nanospheres, gels, scaffolds, sponges, viral particles etc. [61, 62] There are few in human trials looking a stem cells, gene therapy. Percutaneous delivery of allogeneic endothelial cells has shown promise in a small safety study of 21 patients applied at the SFA after angioplasty and stenting.…”

Site-specific thrombolytic and anticoagulant biomaterials

“…A performance improvement in small-diameter bypass grafts remains a clinical objective. Local application of antithrombotic agents in attenuating early fibrin deposition could favourably influence acute graft patency, and may improve long-term graft patency as well [1,2]. A bioactive heparinised graft luminal surface has also been proved successful to improve graft patency in canine interposition models [3].…”